Thymic model for examining BRCA2 expression and function.

Published

Journal Article

Mutations in the human BRCA2 breast cancer susceptibility gene are associated with increased risks of breast, ovarian, and other cancers. BRCA2 has been hypothesized to function in processes of DNA damage/breakage repair, cell proliferation, and apoptosis. These processes continually occur in the thymus during thymocyte development, and BRCA2 mRNA is highly expressed in thymus relative to most other organs. We therefore used the thymus as a model system to study BRCA2 expression and function. Quantitative reverse transcription polymerase chain reaction experiments showed that highly activated immature CD4(+) CD8(+) double-positive human thymocytes that exhibited high levels of proliferation and apoptosis had increased BRCA2 mRNA levels relative to other thymocyte subsets. BRCA2 mRNA levels were upregulated in thymocytes treated with the DNA-damaging agent etoposide. Only modest increases were associated with proliferation in human peripheral lymphocytes in response to concanavalin A (ConA) mitogen. Mice homozygous for a targeted mutation in Brca2 exon 27 (Brca2(Delta27/Delta27)) showed normal thymic architecture but had 18% decreased thymocyte cellularity compared with wild-type mice. Thymocytes from these Brca2(Delta27/Delta27) mice displayed decreased apoptosis in response to etoposide-induced DNA damage compared with wild-type thymocytes. These studies suggest that BRCA2 mRNA levels are modulated during DNA damage and may be important during apoptosis.

Full Text

Duke Authors

Cited Authors

  • Flores, KG; McAllister, KA; Greer, PK; Wiseman, RW; Hale, LP

Published Date

  • November 2002

Published In

Volume / Issue

  • 35 / 3

Start / End Page

  • 103 - 109

PubMed ID

  • 12410562

Pubmed Central ID

  • 12410562

International Standard Serial Number (ISSN)

  • 0899-1987

Digital Object Identifier (DOI)

  • 10.1002/mc.10081

Language

  • eng

Conference Location

  • United States